Kidney stone disease, also known as urolithiasis, is when a solid piece of material (kidney stone) occurs in the urinary tract.[2] Kidney stones typically form in the kidney and leave the body in the urine stream. A small stone may pass without causing symptoms.[2] If a stone grows to more than 5 millimeters (0.2 in) it can cause blockage of the ureter resulting in severe pain in the lower back or abdomen.[2][3] A stone may also result in blood in the urine, vomiting, or painful urination.[2] About half of people will have another stone within ten years.[4]

Between 1% and 15% of people globally are affected by kidney stones at some point in their life.[4] In 2013, 49 million cases occurred,[8] resulting in about 15,000 deaths.[9] They have become more common in the Western world since the 1970s.[4] Generally, more men are affected than women.[2] Kidney stones have affected humans throughout history with descriptions of surgery to remove them dating from as early as 600 BC.[1]

Diagram showing the typical location of renal colic, below the rib cage to just above the pelvis

The hallmark of a stone that obstructs the ureter or renal pelvis is excruciating, intermittent pain that radiates from the flank to the groin or to the inner thigh.[10] This pain, known as renal colic, is often described as one of the strongest pain sensations known.[11] Renal colic caused by kidney stones is commonly accompanied by urinary urgency, restlessness, hematuria, sweating, nausea, and vomiting. It typically comes in waves lasting 20 to 60 minutes caused by peristaltic contractions of the ureter as it attempts to expel the stone.[10] The embryological link between the urinary tract, the genital system, and the gastrointestinal tract is the basis of the radiation of pain to the gonads, as well as the nausea and vomiting that are also common in urolithiasis.[12]Postrenal azotemia and hydronephrosis can be observed following the obstruction of urine flow through one or both ureters.[13] Pain in the lower left quadrant can sometimes be confused with diverticulitis because the sigmoid colon overlaps the ureter and the exact location of the pain may be difficult to isolate due to the close proximity of these two structures.

Calcium is one component of the most common type of human kidney stones, calcium oxalate. Some studies[which?] suggest people who take calcium or vitamin D as a dietary supplement have a higher risk of developing kidney stones. In the United States, kidney stone formation was used as an indicator of excess calcium intake by the Reference Daily Intake committee for calcium in adults.[25]

Unlike supplemental calcium, high intakes of dietary calcium do not appear to cause kidney stones and may actually protect against their development.[16][26] This is perhaps related to the role of calcium in binding ingested oxalate in the gastrointestinal tract. As the amount of calcium intake decreases, the amount of oxalate available for absorption into the bloodstream increases; this oxalate is then excreted in greater amounts into the urine by the kidneys. In the urine, oxalate is a very strong promoter of calcium oxalate precipitation—about 15 times stronger than calcium. A 2004 study found that diets low in calcium are associated with a higher overall risk for kidney stone formation.[27] For most individuals, other risk factors for kidney stones, such as high intakes of dietary oxalates and low fluid intake, play a greater role than calcium intake.[28]

Calcium is not the only electrolyte that influences the formation of kidney stones. For example, by increasing urinary calcium excretion, high dietary sodium may increase the risk of stone formation.[16]

Drinking fluoridated tap water may increase the risk of kidney stone formation by a similar mechanism, though further epidemiologic studies are warranted to determine whether fluoride in drinking water is associated with an increased incidence of kidney stones.[29] High dietary intake of potassium appears to reduce the risk of stone formation because potassium promotes the urinary excretion of citrate, an inhibitor of calcium crystal formation.[citation needed]

Kidney stones are more likely to develop, and to grow larger, if a person has low dietary magnesium. Magnesium inhibits stone formation.[30]

Diets in Western nations typically contain a large proportion of animal protein. Consumption of animal protein creates an acid load that increases urinary excretion of calcium and uric acid and reduced citrate. Urinary excretion of excess sulfurous amino acids (e.g., cysteine and methionine), uric acid, and other acidic metabolites from animal protein acidifies the urine, which promotes the formation of kidney stones.[31] Low urinary citrate excretion is also commonly found in those with a high dietary intake of animal protein, whereas vegetarians tend to have higher levels of citrate excretion.[16] Low urinary citrate, too, promotes stone formation.[31]

The evidence linking vitamin C supplements with an increased rate of kidney stones is inconclusive.[32] The excess dietary intake of vitamin C might increase the risk of calcium oxalate stone formation, in practice this is rarely encountered. The link between vitamin D intake and kidney stones is also tenuous. Excessive vitamin D supplementation may increase the risk of stone formation by increasing the intestinal absorption of calcium; correction of a deficiency does not.[16]

There are no conclusive data demonstrating a cause-and-effect relationship between alcoholic beverage consumption and kidney stones. However, some have theorized that certain behaviors associated with frequent and binge drinking can lead to dehydration, which can in turn lead to the development of kidney stones.[33]

Small crystals formed in kidney. The most common crystals are made of calcium oxalate and they are generally 4–5 mm. Staghorn kidney stones are considerably larger. 1. Calcium and oxalate come together to make the crystal nucleus. Supersaturation promotes their combination (as does inhibition.) 2. Continued deposition at the renal papillae leads to growth of the kidney stones. 3. Kidney stones grow and collect debris. In the case where the kidney stones block all routes to the renal papillae, this can cause severe discomfort. 4. The complete staghorn stone forms and retention occurs. Smaller solids that break off can become trapped in the urinary glands causing discomfort. 5. Displaced stones travel through the ureter. If they cannot be broken down, they must be physically removed by a surgeon.

Hypocitraturia or low urinary citrate excretion (defined as lower than 320 mg/day) can cause kidney stones in up to 2/3 of cases. The protective role of citrate is linked to several mechanisms; in fact citrate reduces urinary supersaturation of calcium salts by forming soluble complexes with calcium ions and by inhibiting crystal growth and aggregation. The therapy with potassium citrate, or magnesium potassium citrate, is commonly prescribed in clinical practice in order to increase urinary citrate and to reduce stone formation rates.[36]

When the urine becomes supersaturated (when the urine solvent contains more solutes than it can hold in solution) with one or more calculogenic (crystal-forming) substances, a seed crystal may form through the process of nucleation.[21] Heterogeneous nucleation (where there is a solid surface present on which a crystal can grow) proceeds more rapidly than homogeneous nucleation (where a crystal must grow in a liquid medium with no such surface), because it requires less energy. Adhering to cells on the surface of a renal papilla, a seed crystal can grow and aggregate into an organized mass. Depending on the chemical composition of the crystal, the stone-forming process may proceed more rapidly when the urine pH is unusually high or low.[37]

Supersaturation of the urine with respect to a calculogenic compound is pH-dependent. For example, at a pH of 7.0, the solubility of uric acid in urine is 158 mg/100 ml. Reducing the pH to 5.0 decreases the solubility of uric acid to less than 8 mg/100 ml. The formation of uric acid stones requires a combination of hyperuricosuria (high urine uric acid levels) and low urine pH; hyperuricosuria alone is not associated with uric acid stone formation if the urine pH is alkaline.[38] Supersaturation of the urine is a necessary, but not a sufficient, condition for the development of any urinary calculus.[21] Supersaturation is likely the underlying cause of uric acid and cystine stones, but calcium-based stones (especially calcium oxalate stones) may have a more complex etiology.[39]

AxialCT scan of abdomen without contrast, showing a 3-mm stone (marked by an arrow) in the left proximal ureter

Diagnosis of kidney stones is made on the basis of information obtained from the history, physical examination, urinalysis, and radiographic studies.[42] Clinical diagnosis is usually made on the basis of the location and severity of the pain, which is typically colicky in nature (comes and goes in spasmodic waves). Pain in the back occurs when calculi produce an obstruction in the kidney.[43] Physical examination may reveal fever and tenderness at the costovertebral angle on the affected side.[42]

In people with a history of stones, those who are less than 50 years of age and are presenting with the symptoms of stones without any concerning signs do not require helical CT scan imaging.[44]

Otherwise a noncontrast helical CT scan with 5 millimeters (0.2 in) sections is the diagnostic modality of choice in the radiographic evaluation of suspected nephrolithiasis.[12][42][45][46][3] All stones are detectable on CT scans except very rare stones composed of certain drug residues in the urine,[47] such as from indinavir. Calcium-containing stones are relatively radiodense, and they can often be detected by a traditional radiograph of the abdomen that includes the kidneys, ureters, and bladder (KUB film).[47] Some 60% of all renal stones are radiopaque.[45][48] In general, calcium phosphate stones have the greatest density, followed by calcium oxalate and magnesium ammonium phosphate stones. Cystine calculi are only faintly radiodense, while uric acid stones are usually entirely radiolucent.[49]

Where a CT scan is unavailable, an intravenous pyelogram may be performed to help confirm the diagnosis of urolithiasis. This involves intravenous injection of a contrast agent followed by a KUB film. Uroliths present in the kidneys, ureters or bladder may be better defined by the use of this contrast agent. Stones can also be detected by a retrograde pyelogram, where a similar contrast agent is injected directly into the distal ostium of the ureter (where the ureter terminates as it enters the bladder).[45]

Ultrasound imaging of the kidneys can sometimes be useful, as it gives details about the presence of hydronephrosis, suggesting the stone is blocking the outflow of urine.[47] Radiolucent stones, which do not appear on KUB, may show up on ultrasound imaging studies. Other advantages of renal ultrasonography include its low cost and absence of radiation exposure. Ultrasound imaging is useful for detecting stones in situations where X-rays or CT scans are discouraged, such as in children or pregnant women.[50] Despite these advantages, renal ultrasonography in 2009 was not considered a substitute for noncontrast helical CT scan in the initial diagnostic evaluation of urolithiasis.[46] The main reason for this is that compared with CT, renal ultrasonography more often fails to detect small stones (especially ureteral stones), as well as other serious disorders that could be causing the symptoms.[10] A 2014 study confirmed that ultrasonography rather than CT as an initial diagnostic test results in less radiation exposure and did not find any significant complications.[51]

collection of stones (by urinating through a StoneScreen kidney stone collection cup or a simple tea strainer) is useful. Chemical analysis of collected stones can establish their composition, which in turn can help to guide future preventive and therapeutic management.

Some of the oxalate in urine is produced by the body. Calcium and oxalate in the diet play a part but are not the only factors that affect the formation of calcium oxalate stones. Dietary oxalate is found in many vegetables, fruits, and nuts. Calcium from bone may also play a role in kidney stone formation.

Scanning electron micrograph of the surface of a kidney stone showing tetragonal crystals of Weddellite (calcium oxalate dihydrate) emerging from the amorphous central part of the stone (the horizontal length of the picture represents 0.5 mm of the figured original)

Oxaluria is increased in patients with certain gastrointestinal disorders including inflammatory bowel disease such as Crohn disease or patients who have undergone resection of the small bowel or small bowel bypass procedures. Oxaluria is also increased in patients who consume increased amounts of oxalate (found in vegetables and nuts). Primary hyperoxaluria is a rare autosomal recessive condition which usually presents in childhood.[57]

Calcium oxalate crystals in urine appear as 'envelopes' microscopically. They may also form 'dumbbells.'[57]

About 5–10% of all stones are formed from uric acid.[17] People with certain metabolic abnormalities, including obesity,[16] may produce uric acid stones. They also may form in association with conditions that cause hyperuricosuria (an excessive amount of uric acid in the urine) with or without hyperuricemia (an excessive amount of uric acid in the serum). They may also form in association with disorders of acid/base metabolism where the urine is excessively acidic (low pH), resulting in precipitation of uric acid crystals. A diagnosis of uric acid urolithiasis is supported by the presence of a radiolucent stone in the face of persistent urine acidity, in conjunction with the finding of uric acid crystals in fresh urine samples.[59]

Urolithiasis refers to stones originating anywhere in the urinary system, including the kidneys and bladder.[12] Nephrolithiasis refers to the presence of such stones in the kidneys. Calyceal calculi refers to aggregations in either the minor or major calyx, parts of the kidney that pass urine into the ureter (the tube connecting the kidneys to the urinary bladder). The condition is called ureterolithiasis when a calculus is located in the ureter. Stones may also form or pass into the bladder, a condition referred to as bladder stones.[66]

Preventative measures depend on the type of stones. In those with calcium stones, drinking lots of fluids, thiazidediuretics and citrate are effective as is allopurinol in those with high uric acid levels in the blood or urine.[67][68]

Specific therapy should be tailored to the type of stones involved. Diet can have a profound influence on the development of kidney stones. Preventive strategies include some combination of dietary modifications and medications with the goal of reducing the excretory load of calculogenic compounds on the kidneys.[27][69][70] Current dietary recommendations to minimize the formation of kidney stones include:[71]

Increasing total fluid intake to more than two liters per day of urine output.

Limiting animal protein intake to no more than two meals daily (an association between animal protein consumption and recurrence of kidney stones has been shown in men[73]).

Limiting consumption of cola soft drinks,[67] which contain phosphoric acid, to less than one liter of soft drink per week.[74]

Maintenance of dilute urine by means of vigorous fluid therapy is beneficial in all forms of nephrolithiasis, so increasing urine volume is a key principle for the prevention of kidney stones. Fluid intake should be sufficient to maintain a urine output of at least 2 litres (68 US fl oz) per day.[68] A high fluid intake has been associated with a 40% reduction in recurrence risk.[46] The quality of the evidence for this, however, is not very good.[68]

Calcium binds with available oxalate in the gastrointestinal tract, thereby preventing its absorption into the bloodstream, and reducing oxalate absorption decreases kidney stone risk in susceptible people.[75] Because of this, some nephrologists and urologists recommend chewing calcium tablets during meals containing oxalate foods.[76] Calcium citrate supplements can be taken with meals if dietary calcium cannot be increased by other means. The preferred calcium supplement for people at risk of stone formation is calcium citrate because it helps to increase urinary citrate excretion.[70]

Aside from vigorous oral hydration and consumption of more dietary calcium, other prevention strategies include avoidance of large doses of supplemental vitamin C and restriction of oxalate-rich foods such as leaf vegetables, rhubarb, soy products and chocolate.[77] However, no randomized, controlled trial of oxalate restriction has yet been performed to test the hypothesis that oxalate restriction reduces the incidence of stone formation.[76] Some evidence indicates magnesium intake decreases the risk of symptomatic nephrolithiasis.[77]

The mainstay for medical management of uric acid stones is alkalinization (increasing the pH) of the urine. Uric acid stones are among the few types amenable to dissolution therapy, referred to as chemolysis. Chemolysis is usually achieved through the use of oral medications, although in some cases, intravenous agents or even instillation of certain irrigating agents directly onto the stone can be performed, using antegrade nephrostomy or retrograde ureteral catheters.[38]Acetazolamide (Diamox) is a medication that alkalinizes the urine. In addition to acetazolamide or as an alternative, certain dietary supplements are available that produce a similar alkalinization of the urine. These include sodium bicarbonate, potassium citrate, magnesium citrate, and Bicitra (a combination of citric acid monohydrate and sodium citrate dihydrate).[78] Aside from alkalinization of the urine, these supplements have the added advantage of increasing the urinary citrate level, which helps to reduce the aggregation of calcium oxalate stones.[38]

Increasing the urine pH to around 6.5 provides optimal conditions for dissolution of uric acid stones. Increasing the urine pH to a value higher than 7.0 increases the risk of calcium phosphate stone formation. Testing the urine periodically with nitrazine paper can help to ensure the urine pH remains in this optimal range. Using this approach, stone dissolution rate can be expected to be around 10 mm (0.4 in) of stone radius per month.[38]

One of the recognized medical therapies for prevention of stones is the thiazide and thiazide-like diuretics, such as chlorthalidone or indapamide. These drugs inhibit the formation of calcium-containing stones by reducing urinary calcium excretion.[10] Sodium restriction is necessary for clinical effect of thiazides, as sodium excess promotes calcium excretion. Thiazides work best for renal leak hypercalciuria (high urine calcium levels), a condition in which high urinary calcium levels are caused by a primary kidney defect. Thiazides are useful for treating absorptive hypercalciuria, a condition in which high urinary calcium is a result of excess absorption from the gastrointestinal tract.[40]

For people with hyperuricosuria and calcium stones, allopurinol is one of the few treatments that have been shown to reduce kidney stone recurrences. Allopurinol interferes with the production of uric acid in the liver. The drug is also used in people with gout or hyperuricemia (high serum uric acid levels).[79] Dosage is adjusted to maintain a reduced urinary excretion of uric acid. Serum uric acid level at or below 6 mg/100 ml) is often a therapeutic goal. Hyperuricemia is not necessary for the formation of uric acid stones; hyperuricosuria can occur in the presence of normal or even low serum uric acid. Some practitioners advocate adding allopurinol only in people in whom hyperuricosuria and hyperuricemia persist, despite the use of a urine-alkalinizing agent such as sodium bicarbonate or potassium citrate.[38]

Stone size influences the rate of spontaneous stone passage. For example, up to 98% of small stones (less than 5 mm (0.2 in) in diameter) may pass spontaneously through urination within four weeks of the onset of symptoms,[3] but for larger stones (5 to 10 mm (0.2 to 0.4 in) in diameter), the rate of spontaneous passage decreases to less than 53%.[80] Initial stone location also influences the likelihood of spontaneous stone passage. Rates increase from 48% for stones located in the proximal ureter to 79% for stones located at the vesicoureteric junction, regardless of stone size.[80] Assuming no high-grade obstruction or associated infection is found in the urinary tract, and symptoms are relatively mild, various nonsurgical measures can be used to encourage the passage of a stone.[38] Repeat stone formers benefit from more intense management, including proper fluid intake and use of certain medications. In addition, careful surveillance is clearly required to maximize the clinical course for people who are stone formers.[81]

Management of pain often requires intravenous administration of NSAIDs or opioids.[10] Orally administered medications are often effective for less severe discomfort.[50] The use of antispasmodics do not have further benefit.[6]

The use of medications to speed the spontaneous passage of stones in the ureter is referred to as medical expulsive therapy.[82][83] Several agents, including alpha adrenergic blockers (such as tamsulosin) and calcium channel blockers (such as nifedipine), have been found to be effective.[82] Alpha blockers appear to lead to both higher and faster stone clearance rates.[84] Alpha blockers; however, only appear to be effective for stones over 4 mm but less than 10 mm in size.[85] A combination of tamsulosin and a corticosteroid may be better than tamsulosin alone.[82] These treatments also appear to be a useful in addition to lithotripsy.[3]

Extracorporeal shock wave lithotripsy (ESWL) is a noninvasive technique for the removal of kidney stones. Most ESWL is carried out when the stone is present near the renal pelvis. ESWL involves the use of a lithotriptor machine to deliver externally applied, focused, high-intensity pulses of ultrasonic energy to cause fragmentation of a stone over a period of around 30–60 minutes. Following its introduction in the United States in February 1984, ESWL was rapidly and widely accepted as a treatment alternative for renal and ureteral stones.[86] It is currently used in the treatment of uncomplicated stones located in the kidney and upper ureter, provided the aggregate stone burden (stone size and number) is less than 20 mm (0.8 in) and the anatomy of the involved kidney is normal.[87][88] For a stone greater than 10 mm (0.4 in), ESWL may not help break the stone in one treatment; instead, two or three treatments may be needed. Some 80 to 85% of simple renal calculi can be effectively treated with ESWL.[3] A number of factors can influence its efficacy, including chemical composition of the stone, presence of anomalous renal anatomy and the specific location of the stone within the kidney, presence of hydronephrosis, body mass index, and distance of the stone from the surface of the skin.[86] Common adverse effects of ESWL include acute trauma, such as bruising at the site of shock administration, and damage to blood vessels of the kidney.[89][90] In fact, the vast majority of people who are treated with a typical dose of shock waves using currently accepted treatment settings are likely to experience some degree of acute kidney injury.[86] ESWL-induced acute kidney injury is dose-dependent (increases with the total number of shock waves administered and with the power setting of the lithotriptor) and can be severe,[86] including internal bleeding and subcapsular hematomas. On rare occasions, such cases may require blood transfusion and even lead to acute renal failure. Hematoma rates may be related to the type of lithotriptor used; hematoma rates of less than 1% and up to 13% have been reported for different lithotriptor machines.[90] Recent studies show reduced acute tissue injury when the treatment protocol includes a brief pause following the initiation of treatment, and both improved stone breakage and a reduction in injury when ESWL is carried out at slow shock wave rate.[86]

In addition to the aforementioned potential for acute kidney injury, animal studies suggest these acute injuries may progress to scar formation, resulting in loss of functional renal volume.[89][90] Recent prospective studies also indicate elderly people are at increased risk of developing new-onset hypertension following ESWL. In addition, a retrospective case-control study published by researchers from the Mayo Clinic in 2006 has found an increased risk of developing diabetes mellitus and hypertension in people who had undergone ESWL, compared with age and gender-matched people who had undergone nonsurgical treatment. Whether or not acute trauma progresses to long-term effects probably depends on multiple factors that include the shock wave dose (i.e., the number of shock waves delivered, rate of delivery, power setting, acoustic characteristics of the particular lithotriptor, and frequency of retreatment), as well as certain intrinsic predisposing pathophysiologic risk factors.[86]

To address these concerns, the American Urological Association established the Shock Wave Lithotripsy Task Force to provide an expert opinion on the safety and risk-benefit ratio of ESWL. The task force published a white paper outlining their conclusions in 2009. They concluded the risk-benefit ratio remains favorable for many people.[86] The advantages of ESWL include its noninvasive nature, the fact that it is technically easy to treat most upper urinary tract calculi, and that, at least acutely, it is a well-tolerated, low-morbidity treatment for the vast majority of people. However, they recommended slowing the shock wave firing rate from 120 pulses per minute to 60 pulses per minute to reduce the risk of renal injury and increase the degree of stone fragmentation.[86]

Most stones under 5 mm (0.2 in) pass spontaneously.[27][3] Prompt surgery may, nonetheless, be required in persons with only one working kidney, bilateral obstructing stones, a urinary tract infection and thus, it is presumed, an infected kidney, or intractable pain.[91] Beginning in the mid-1980s, less invasive treatments such as extracorporeal shock wave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy began to replace open surgery as the modalities of choice for the surgical management of urolithiasis.[3] More recently, flexible ureteroscopy has been adapted to facilitate retrograde nephrostomy creation for percutaneous nephrolithotomy. This approach is still under investigation, though early results are favorable.[92] Percutaneous nephrolithotomy or, rarely, anatrophic nephrolithotomy, is the treatment of choice for large or complicated stones (such as calyceal staghorn calculi) or stones that cannot be extracted using less invasive procedures.[42][3]

A kidney stone at the tip of an ultrasonic stone disintegration apparatus

Ureteroscopy has become increasingly popular as flexible and rigid fiberoptic ureteroscopes have become smaller. One ureteroscopic technique involves the placement of a ureteral stent (a small tube extending from the bladder, up the ureter and into the kidney) to provide immediate relief of an obstructed kidney. Stent placement can be useful for saving a kidney at risk for postrenal acute renal failure due to the increased hydrostatic pressure, swelling and infection (pyelonephritis and pyonephrosis) caused by an obstructing stone. Ureteral stents vary in length from 24 to 30 cm (9.4 to 11.8 in) and most have a shape commonly referred to as a "double-J" or "double pigtail", because of the curl at both ends. They are designed to allow urine to flow past an obstruction in the ureter. They may be retained in the ureter for days to weeks as infections resolve and as stones are dissolved or fragmented by ESWL or by some other treatment. The stents dilate the ureters, which can facilitate instrumentation, and they also provide a clear landmark to aid in the visualization of the ureters and any associated stones on radiographic examinations. The presence of indwelling ureteral stents may cause minimal to moderate discomfort, frequency or urgency incontinence, and infection, which in general resolves on removal. Most ureteral stents can be removed cystoscopically during an office visit under topical anesthesia after resolution of the urolithiasis.[93]

More definitive ureteroscopic techniques for stone extraction (rather than simply bypassing the obstruction) include basket extraction and ultrasound ureterolithotripsy. Laser lithotripsy is another technique, which involves the use of a holmium:yttrium aluminium garnet (Ho:YAG) laser to fragment stones in the bladder, ureters, and kidneys.[94]

Ureteroscopic techniques are generally more effective than ESWL for treating stones located in the lower ureter, with success rates of 93–100% using Ho:YAG laser lithotripsy.[80] Although ESWL has been traditionally preferred by many practitioners for treating stones located in the upper ureter, more recent experience suggests ureteroscopic techniques offer distinct advantages in the treatment of upper ureteral stones. Specifically, the overall success rate is higher, fewer repeat interventions and postoperative visits are needed, and treatment costs are lower after ureteroscopic treatment when compared with ESWL. These advantages are especially apparent with stones greater than 10 mm (0.4 in) in diameter. However, because ureteroscopy of the upper ureter is much more challenging than ESWL, many urologists still prefer to use ESWL as a first-line treatment for stones of less than 10 mm, and ureteroscopy for those greater than 10 mm in diameter.[80] Ureteroscopy is the preferred treatment in pregnant and morbidly obese people, as well as those with bleeding disorders.[3]

Kidney stones affect all geographical, cultural, and racial groups. The lifetime risk is about 10 to 15% in the developed world, but can be as high as 20 to 25% in the Middle East. The increased risk of dehydration in hot climates, coupled with a diet 50% lower in calcium and 250% higher in oxalates compared to Western diets, accounts for the higher net risk in the Middle East.[96] In the Middle East, uric acid stones are more common than calcium-containing stones.[21] The number of deaths due to kidney stones is estimated at 19,000 per year being fairly consistent between 1990 and 2010.[97]

In North America and Europe, the annual number of new cases per year of kidney stones is roughly 0.5%. In the United States, the frequency in the population of urolithiasis has increased from 3.2% to 5.2% from the mid-1970s to the mid-1990s.[17] In the United States, about 9% of the population has had a kidney stone.[2]

The total cost for treating urolithiasis was US$2 billion in 2003.[47] About 65–80% of those with kidney stones are men; most stones in women are due to either metabolic defects (such as cystinuria) or infection.[58][98] (p. 1057) Men most commonly experience their first episode between 30 and 40 years of age, whereas for women, the age at first presentation is somewhat later.[58] The age of onset shows a bimodal distribution in women, with episodes peaking at 35 and 55 years.[47] Recurrence rates are estimated at 50% over a 10-year and 75% over 20-year period,[17] with some people experiencing ten or more episodes over the course of a lifetime.[58]

The existence of kidney stones was first recorded thousands of years ago, and lithotomy for the removal of stones is one of the earliest known surgical procedures.[99] In 1901, a stone discovered in the pelvis of an ancient Egyptian mummy was dated to 4,800 BC. Medical texts from ancient Mesopotamia, India, China, Persia, Greece, and Rome all mentioned calculous disease. Part of the Hippocratic Oath suggests there were practicing surgeons in ancient Greece to whom physicians were to defer for lithotomies. The Roman medical treatise De Medicina by Aulus Cornelius Celsus contained a description of lithotomy,[100] and this work served as the basis for this procedure until the 18th century.[101]

New techniques in lithotomy began to emerge starting in 1520, but the operation remained risky. After Henry Jacob Bigelow popularized the technique of litholapaxy in 1878,[103] the mortality rate dropped from about 24% to 2.4%. However, other treatment techniques continued to produce a high level of mortality, especially among inexperienced urologists.[101][102] In 1980, Dornier MedTech introduced extracorporeal shock wave lithotripsy for breaking up stones via acoustical pulses, and this technique has since come into widespread use.[86]

Crystallization of calcium oxalate appears to be inhibited by certain substances in the urine that retard the formation, growth, aggregation, and adherence of crystals to renal cells. By purifying urine using salt precipitation, isoelectric focusing, and size-exclusion chromatography, some researchers have found that calgranulin, a protein formed in the kidney, is a potent inhibitor of the in vivo formation of calcium oxalate crystals. Considering its extremely high levels of inhibition of growth and aggregation of calcium oxalate crystals, calgranulin might be an important intrinsic factor in the prevention of nephrolithiasis.[104]

Although kidney stones do not often occur in children, the incidence is increasing.[105] These stones are in the kidney in two thirds of reported cases, and in the ureter in the remaining cases. Older children are at greater risk independent of age and sex.[106]

As with adults, most pediatric kidney stones are predominantly composed of calcium oxalate; struvite and calcium phosphate stones are less common. Calcium oxalate stones in children are associated with high amounts of calcium, oxalate, and magnesium in acidic urine.[107]

Among ruminants, uroliths more commonly cause problems in males than in females; the sigmoid flexure of the ruminant male urinary tract is more likely to obstruct passage. Early-castrated males are at greater risk, because of lesser urethral diameter.[108]

Differing generalizations regarding effects of pH on formation of silicate uroliths may be found.[108][110] In this connection, it may be noted that under some circumstances, calcium carbonate accompanies silica in siliceous uroliths.[111]

Pelleted feeds may be conducive to formation of phosphate uroliths, because of increased urinary phosphorus excretion. This is attributable to lower saliva production where pelleted rations containing finely ground constituents are fed. With less blood phosphate partitioned into saliva, more tends to be excreted in urine.[112] (Most saliva phosphate is fecally excreted.[113])

Oxalate uroliths can occur in ruminants, although such problems from oxalate ingestion may be relatively uncommon. Ruminant urolithiasis associated with oxalate ingestion has been reported.[114] However, no renal tubular damage or visible deposition of calcium oxalate crystals in kidneys was found in yearling wether sheep fed diets containing soluble oxalate at 6.5 percent of dietary dry matter for about 100 days.[115]

Various surgical interventions, e.g. amputation of the urethral process at its base near the glans penis in male ruminants, perineal urethrostomy, or tube cystostomy may be considered for relief of obstructive urolithiasis.[116]

^Scott, D. and W. Buchan. 1988. The effects of feeding pelleted diets made from either coarsely or finely ground hay on phosphorus balance and on the partition of phosphorus excretion between urine and faeces in the sheep. Q. J. Exp. Physiol. 73: 315-322.